Typical Treatment of Chronic Lymphocytic Leukemia

Treatment options for chronic lymphocytic leukemia (CLL) vary greatly, depending on the person’s age, the disease risk group, and the reason for treating (for example, which symptoms it is causing). Many people live a long time with CLL, but in general it is very difficult to cure, and early treatment hasn't been shown to help people live longer. Because of this and because treatment can cause side effects, doctors often advise waiting until the disease is progressing or bothersome symptoms appear, before starting treatment.

If treatment is needed, factors that should be taken into account include the patient’s age, general health, and prognostic factors such as the presence of deletions in chromosomes 17 or 11, or high levels of ZAP-70 and CD38.

Initial treatment of CLL

Drugs that may be used

Patients who might not be able to tolerate the side effects of strong chemotherapy (chemo) are often treated with chlorambucil with a monoclonal antibody like obinutuzumab (Gazyva®). Other options include ibrutinib (Imbruvica®) alone, and rituximab alone or with a corticosteroid like prednisone. There are other options, too.

In stronger and healthier patients, commonly used treatments include:

  • FCR: fludarabine (Fludara®), cyclophosphamide (Cytoxan®), and rituximab
  • Bendamustine (sometimes with a CD20 monoclonal antibody )
  • Ibrutinib
  • FR: fludarabine and rituximab
  • High-dose prednisone and rituximab
  • PCR: pentostatin (Nipent®), cyclophosphamide, and rituximab
  • Alemtuzumab (Campath®) with rituximab

Other drugs or combinations of drugs may also be used.

Radiation or surgery

If the only problem is an enlarged spleen or swollen lymph nodes in one part of the body, localized treatment with low-dose radiation therapy may be used. Splenectomy (surgery to remove the spleen) is another option if the enlarged spleen is causing symptoms.

Leukapheresis

Sometimes very high numbers of CLL cells in the blood cause problems with normal circulation. This is called leukostasis. Chemo may not lower the number of cells until a few days after the first dose, so before the chemo is given, some of the cells may need to be removed from the blood with a procedure called leukapheresis. This treatment lowers blood counts right away. The effect lasts only for a short time, but it may help until the chemo has a chance to work. Leukapheresis is also sometimes used before chemo if there are very high numbers of leukemia cells (even when they aren’t causing problems) to prevent tumor lysis syndrome. (This was discussed in the chemotherapy section.)

Transplant

Some people who have very high-risk disease (based on prognostic factors ) may be referred for possible stem cell transplant (SCT) early in treatment.

Second-line treatment of CLL

If the initial treatment is no longer working or the disease comes back, another type of treatment often helps. If the initial response to the treatment lasted a long time (usually at least a few years), the same treatment might be used again. If the initial response wasn't long-lasting, using the same treatment isn't as likely to be helpful. The options will depend on what the first-line treatment was and how well it worked, as well as the person's overall health.

Many of the drugs and combinations listed above may be options as second-line treatments, too. Targeted therapy and monoclonal antibody drugs are commonly used, alone or in combination. Other chemo drugs may also be tried.

If the leukemia responds, stem cell transplant may be an option for some patients.

Some people may have a good response to first-line treatment (such as fludarabine) but may still have some evidence of a small number of leukemia cells in the blood, bone marrow, or lymph nodes. This is known as minimal residual disease. CLL can't be cured, so doctors aren't sure if further treatment right away will be helpful. Some small studies have shown that alemtuzumab can sometimes help get rid of these remaining cells, but it's not yet clear if this improves survival.

Treating complications of CLL

One of the most serious complications of CLL is a change (transformation) of the leukemia to a high-grade or aggressive type of non-Hodgkin lymphoma (NHL) called diffuse large B-cell lymphoma (DLBCL) or to Hodgkin lymphoma. This happens in 2% to 10% of CLL cases, and is known as Richter's transformation. Treatment is often the same as it would be for lymphoma and might include stem cell transplant, because these cases are often hard to treat.

Less often, CLL may progress to prolymphocytic leukemia. As with Richter syndrome, this, too, can be hard to treat. Some studies have suggested that certain drugs such as cladribine (2-CdA) and alemtuzumab may be helpful.

In rare patients with CLL, the leukemia transforms into acute lymphocytic leukemia (ALL). If this happens, treatment is likely to be similar to that used for patients with ALL. 

Acute myeloid leukemia (AML) is another rare complication in patients who have been treated for CLL. Drugs such as chlorambucil and cyclophosphamide can damage the DNA of blood-forming cells. These damaged cells may go on to become cancer, leading to AML, which is very aggressive and often hard to treat.

CLL can cause problems with low blood counts and infections. These are discussed in Supportive Care in Chronic Lymphocytic Leukemia.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

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National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)–Health Professional Version. February 7, 2018. Accessed at www.cancer.gov/types/leukemia/hp/cll-treatment-pdq on April 17, 2018.

National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 5.2018 -- March 26, 2018. Accessed at www.nccn.org/professionals/physician_gls/pdf/cll.pdf on April 17, 2018.

Rafei H, Kharfan-Dabaja MA. Treatment of Del17p and/or aberrant TP53 chronic lymphocytic leukemia in the era of novel therapies. Hematol Oncol Stem Cell Ther. 2018;11:1-12.

 

Last Medical Review: May 10, 2018 Last Revised: May 10, 2018

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